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PMID: 17229474 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Functional characterization of APOBEC-1 complementation factor phosphorylation sites.

Biochimica et biophysica acta ·Vol. 1773 ·No. 3 ·2007-03-00 ·Pages 408-18

Lehmann DM, Galloway CA, MacElrevey C, Sowden MP, Wedekind JE, Smith HC

Abstract

ApoB mRNA editing involves site-specific deamination of cytidine 6666 producing an in-frame translation stop codon. Editing minimally requires APOBEC-1 and APOBEC-1 complementation factor (ACF). Metabolic stimulation of apoB mRNA editing in hepatocytes is associated with serine phosphorylation of ACF localized to editing competent, nuclear 27S editosomes. We demonstrate that activation of protein kinase C (PKC) stimulated editing and enhanced ACF phosphorylation in rat primary hepatocytes. Conversely, activation of protein kinase A (PKA) had no effect on editing. Recombinant PKC efficiently phosphorylated purified ACF64 protein in vitro, whereas PKA did not. Mutagenesis of predicted PKC phosphorylation sites S154 and S368 to alanine inhibited ethanol-stimulated induction of editing suggesting that these sites function in the metabolic regulation of editing. Consistent with this interpretation, substitution of S154 and S368 with aspartic acid stimulated editing to levels comparable to ethanol treatment in control McArdle RH7777 cells. These data suggest that phosphorylation of ACF by PKC may be a key regulatory mechanism of apoB mRNA editing in rat hepatocytes.

MeSH Terms
Amino Acid Sequence Animals Apolipoproteins B/genetics Cells, Cultured Enzyme Activation Hepatocytes/metabolism Heterogeneous-Nuclear Ribonucleoproteins/genetics,metabolism Humans Male Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Phosphorylation Protein Kinases/metabolism Protein Structure, Tertiary RNA, Messenger/genetics Rats Rats, Sprague-Dawley Sequence Alignment
Chemicals
APOBEC-1 complementation factor, rat Apolipoproteins B Heterogeneous-Nuclear Ribonucleoproteins RNA, Messenger Protein Kinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Lehmann David M
Environmental Health Sciences Center, Department of Toxicology, University of Rochester, Rochester, NY 14642, USA.
Galloway Chad A
MacElrevey Celeste
Sowden Mark P
Wedekind Joseph E
Smith Harold C
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Article Info
Journal
Biochimica et biophysica acta
Abbr.
Biochim Biophys Acta
ISSN
0006-3002
DOI
10.1016/j.bbamcr.2006.11.019
Published
2007-03-00
Epub
2006-00-08
Pages
408-18
Language
English
Region
Netherlands
NLM ID
0217513
PMCID
PMC1847399
Subset
IM
Grants
NCRR NIH HHS · RR15934 · United States
NIDDK NIH HHS · DK43739 · United States
NIGMS NIH HHS · GM63162 · United States
NIDDK NIH HHS · R01 DK043739 · United States
NIEHS NIH HHS · 5T32 ES07026 · United States
NIGMS NIH HHS · T32 GM068411 · United States
NIGMS NIH HHS · R01 GM063162 · United States
NIGMS NIH HHS · 5T32 GM068411 · United States
NIEHS NIH HHS · T32 ES007026 · United States
External Links
PubMed source DOI: 10.1016/j.bbamcr.2006.11.019 PMC Full Text
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